Retatrutide

The Next Generation Incretin

Retatrutide (LY3437943) is a novel triple agonist peptide targeting three key metabolic receptors simultaneously: GLP-1, GIP, and glucagon receptors. This triple mechanism represents the cutting edge of incretin-based metabolic research—going beyond dual agonists like tirzepatide to engage an additional pathway.

Eli Lilly's clinical development program has generated significant research interest, with Phase 3 trials ongoing for metabolic applications.

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Why Triple Agonism Matters

Each receptor contributes distinct metabolic effects:

Receptor	Primary Effects	Retatrutide Activity
GLP-1	Glucose regulation, appetite, gastric emptying	Full agonist
GIP	Insulin secretion, fat metabolism, bone health	Full agonist
Glucagon	Energy expenditure, lipid oxidation, hepatic metabolism	Partial agonist

The addition of glucagon receptor agonism distinguishes retatrutide from GLP-1/GIP dual agonists, potentially enhancing energy expenditure and liver-specific metabolic effects.

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Research Focus Areas

Retatrutide is being studied for its potential effects on:

• Body weight regulation — multi-pathway appetite and metabolism control
• Glucose homeostasis — blood sugar management mechanisms
• Energy expenditure — glucagon-mediated thermogenesis
• Hepatic lipid metabolism — liver fat reduction pathways
• Cardiovascular parameters — metabolic syndrome markers
• Incretin signaling — comparative studies vs. mono/dual agonists
• Satiety mechanisms — central and peripheral appetite regulation

Clinical trial data has shown retatrutide producing significant effects on body weight parameters in Phase 2 studies, driving substantial research interest.

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Clinical Development Context

• Developer: Eli Lilly and Company
• Phase: Phase 3 trials ongoing (as of 2024)
• Trial names: TRIUMPH program
• Published data: Phase 2 results in NEJM (2023)

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Technical Specifications

• Synonyms: LY3437943
• Class: GLP-1/GIP/Glucagon triple receptor agonist
• Molecular Weight: ~4,700 g/mol
• Form: Sterile lyophilized powder
• Structure: Modified peptide with fatty acid chain for extended half-life

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Storage & Handling

• Lyophilized: Store at -20°C
• Reconstituted: Store at 2–8°C
• Protect from light and moisture
• Avoid repeated freeze-thaw cycles

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